SUPPLEMENT PROJECT SUMMARY Eye Determinants of Cognition (EyeDOC) Study Rationale: Dementia and mild cognitive impairment (MCI) pose enormous health and societal costs in our aging US population. While cerebral neural loss is known to contribute to Alzheimer's dementia, vascular diseases may contribute substantially to the total burden of dementia and its precursor, MCI. Small-vessel cerebrovascular changes, which are most strongly associated with cognitive impairments, are difficult to detect with brain imaging. However, recent technological advances in ocular coherence tomography (OCT) provide refined measures of the microvascular pathology and neurodegeneration of retinal ganglion cells which may provide sensitive biomarkers reflecting underlying cerebral processes. Design: The EyeDOC study is nested in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS), recruiting 1,000 participants (50% African-American) from two ARIC-NCS field sites (Jackson MS and Washington County, MD) to take part in a comprehensive vision assessment with photographic and OCT imaging of the retina. We will add 209 males to our total recruitment numbers to compensate for lower male representation in this older population. Exposures: EyeDOC will contribute novel ocular measures to the rich ARIC NCS data including: A. Degree of neurodegeneration marked by loss/thinning of the macular ganglion cell complex [GCC] and the retinal nerve fiber layer [NFL] just outside the optic nerve head B. Degree of microvascular pathology marked by a lower macular vessel density in the superficial and deep layers of the retina. Outcomes: The late life cognitive outcomes available from ARIC-NCS include: A. Decline in global cognitive ability, executive function/processing speed, memory, and language ? assessed using neurocognitive testing in V5, V6 and V7. B. Incidence of MCI, which was diagnosed in approximately 20% of the cohort in V5 and is expected to affect a larger percentage at V6 and V7 due to advancing age of the cohort. Aims: This supplement focuses on adding to our ability to understand the impact of potential important sex differences in relationships between retinal measures of neuronal and microvascular health and cognitive impairment. We will also evaluate OCT-derived measures of retinal microvascular health as robust surrogates of microvascular pathology in the brain related to cognitive disease. We will add a cross software platform comparison to our assessment of reproducibility of OCT measures and evaluate the extent to which image quality impacts OCT measures and associated measurement noise. Summary: The EyeDOC study aims to demonstrate the potential of retinal biomarkers to inform the etiology of observed cognitive changes.